Studies conducted with F1 and F2 progeny of crosses between strains of inbred mice that differ greatly in their capacity to make an antibody response to Type III pneumococcal polysaccharide (SSS-III), bacterial (Leuconostoc) dextran B-1355, and lipopolysaccharide from Escherichia coli 0113 (LPS 0113) showed that multiple genes influence the magnitude of the antibody response to these antigens. Other studies using hybrids derived from crosses between C3/HeJ, CBA/N, and RIIIS/J mice indicated that the genetic defects characteristic of these strains of mice are dissimilar and unlinked, and that autosomal, as well as X-linked, genes control the magnitude of serum IgM levels in unimmunized mice.